Abstract: Introduction: Minimal residual disease (MRD) status reflects depth of response and informs prognosis after first-line therapy in patients (pts) with follicular lymphoma (FL). In the GALLIUM study (NCT01332968), the primary endpoint of investigator (INV)-assessed progression-free survival (PFS) in previously untreated FL pts was significantly improved with obinutuzumab (GA101; G)- versus rituximab (R)-based immunochemotherapy treatment. We previously reported consistently higher MRD response rates with G- versus R-based treatment at the end of induction (EOI) (92% vs 85%, respectively; p=0.0041; Pott et al. ASH 2016). Here we report the correlation of MRD response at EOI with updated PFS data and the results of MRD response assessment during maintenance treatment and follow-up. We also assessed MRD responses and outcome in pts who remained MRD-positive at EOI. Methods: Previously untreated pts aged ≥18 years with FL requiring treatment were randomized 1:1 to receive 6-8 cycles of G (1000mg IV on days [D] 1, 8, and 15 of cycle [C] 1 and D1 of C2-6 or 8) or R (375mg/m2 IV on D1) plus standard chemotherapy (CHOP, CVP, or bendamustine). Responding pts received the same antibody as maintenance every 2 months for up to 2 years. MRD status was assessed by real-time quantitative (RQ)-PCR assays at mid-induction (MI) in peripheral blood (PB), at EOI in PB and bone marrow, at 4-monthly intervals during maintenance in PB, and at 6-monthly intervals during follow-up in PB, and was defined as negative (MRD response) if RQ-PCR and subsequent nested PCR were negative in all samples analyzed at the respective time point. INV-assessed PFS was estimated using Kaplan-Meier methods (data cut-off, February 12, 2018). Pts were included in the various analyses if they had evaluable MRD data and achieved a complete or partial response at EOI. Results: After 57 months' median follow-up, MRD evaluable pts (n=634/1202 randomized FL pts) who had a MRD-negative response at EOI (n=564) continued to have a longer PFS than those who had a MRD-positive response at EOI (n=70; hazard ratio 0.38; 95% confidence interval 0.26, 0.56; p 〈 0.0001; Figure 1), which was irrespective of treatment arm (Figure 2). Of the MRD evaluable pts who continued on maintenance treatment, a MRD-negative response was observed at EOI in 300/324 (92.6%) pts in the G arm versus 264/310 (85.2%) in the R arm (p=0.0034). The majority of the MRD-negative pts remained negative during maintenance. No difference in the MRD relapse rate (conversion to MRD positivity) was observed between pts treated with G or R maintenance (6.3% vs 6.1%, respectively). Two-thirds of MRD-negative responses were sustained throughout the maintenance period (G, 67.0%; R, 63.2%), with a rate of disease progression or death of 11.4% in the G arm and 15.5% in the R arm. Twenty-four pts in the G-chemo arm and 46 pts in the R-chemo arm were MRD positive at EOI but eligible for maintenance treatment based on clinical (CT-based) response. Of these, 22 (92%) pts in the G-chemo arm (18 within the first 4 months of maintenance treatment) and 36 (78%) pts in the R-chemo arm (27 within the first 4 months) achieved MRD negativity during maintenance. Of the 12 pts who never achieved an MRD response, 8 progressed or died within 7 months of EOI, 1 progressed after 15 months, 1 progressed after 26 months, and 2 remained MRD positive during maintenance up to month 8 and month 12, respectively, but had no documented tumor progression until D1348 and D1709. Conclusions: These data confirm the prognostic value of MRD status at EOI in previously untreated FL pts receiving immunochemotherapy. Analysis of MRD kinetics revealed that most of the pts who achieved MRD negativity at EOI sustained their responses during maintenance. The majority of pts who were MRD positive at EOI achieved MRD negativity during the first 4 months of maintenance. While this is likely to be indicative of the efficacy of continued treatment, it also suggests that response kinetics can be slower than in those pts who have an early MRD response at MI, and that responses that are beyond the sensitivity of the MRD assay may be less deep. Importantly, pts who failed to achieve MRD negativity at EOI or during early maintenance had a high chance of experiencing early progression or death. These data demonstrate the prognostic value of MRD response assessments in previously untreated FL pts receiving immunochemotherapy. Disclosures Hoster: F. Hoffman-La Roche: Other: Travel support, Research Funding; Roche Pharma AG: Other: Travel support, Research Funding. Unterhalt:F. Hoffman-La Roche: Other: Travel support. van der Jagt:F. Hoffman-La Roche Ltd: Employment, Honoraria, Research Funding. Janssens:Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Ad board, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi-Genzyme: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Ad board, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Kneba:Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Mayer:Affimed: Research Funding; Roche: Research Funding; Johnson & Johnson: Research Funding; Eisai: Research Funding; Novartis: Research Funding. Pocock:Kent & Canterbury Hospital: Employment. Knapp:Roche: Employment. Danesi:F. Hoffmann-La Roche Ltd: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Brown:PAREXEL, external business partner with Roche Products Ltd, Welwyn, UK: Employment. Mundt:Roche: Employment, Other: Ownership interests PLC. Marcus:Gilead: Consultancy; F. Hoffman-La Roche: Other: Travel support and lecture fees; Roche: Consultancy, Other: Travel support and lecture fees . Hiddemann:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: Background: Minimal residual disease (MRD) status reflects treatment efficacy and may predict prognosis after first-line therapy in patients (pts) with follicular lymphoma (FL). GALLIUM (NCT01332968) is an ongoing, randomized global Phase 3 study evaluating the efficacy and safety of obinutuzumab (GA101; GAZYVA/GAZYVARO; G) vs rituximab (R) as induction (with chemotherapy [chemo]; bendamustine, CHOP or CVP) and maintenance (in responders) in previously untreated pts with indolent non-Hodgkin lymphoma. In GALLIUM, the primary endpoint of investigator-assessed PFS in pts with FL was significantly improved with G- vs R-based treatment. We report the results of MRD assessment at mid induction (MI) and end of induction (EOI) in FL pts in GALLIUM. Methods: Diagnostic peripheral blood (PB) and bone marrow (BM) samples from FL pts were screened by consensus PCR to detect a t(14;18) translocation and/or clonal Ig variable domain rearrangement suitable for MRD assessment. In pts with a detectable clonal marker, allele- or translocation-specific real-time quantitative (RQ)-PCR assays were designed with a sensitivity ≤10-4. RQ-PCR data were evaluated by European Study Group criteria for MRD detection (van der Velden, Leukemia 2007). MRD status was assessed at MI in PB, and at EOI in PB and BM, and defined as negative (MRD response) if RQ-PCR and subsequent nested PCR were negative in all samples analyzed at the respective time point. Results: Of the 1202 FL pts enrolled in GALLIUM, 1138 provided consent for MRD analyses. Baseline PB or BM samples were available for 1101 pts; a clonal marker was detected in 968 (88%) of these pts and 815 (74%) had an RQ-PCR assay fulfilling sensitivity criteria. Pts with a detectable clonal marker had baseline characteristics comparable to pts without a marker, with the exception of higher-stage disease (61% vs 34% Ann Arbor stage IV), reflecting increased BM involvement. Among 696 pts with an available PB or BM sample at EOI, MRD response was significantly higher in the G-chemo arm than the R-chemo arm (92% vs 85%; p=0.0041; Table 1). BM clearance of residual tumor cells at EOI was higher in the G-chemo vs R-chemo arm (93% [199/214] vs 83% [165/200]; p=0.0014), whereas PB clearance at EOI was similarly high in both arms (96% [323/336] vs 94% [320/341]; p=0.22). MRD clearance occurred early during treatment: at MI, 94% of pts in the G-chemo arm achieved MRD-negative status in PB compared with 89% in the R-chemo arm (p=0.013; Table 2). The anti-lymphoma activity of G-chemo induction was confirmed by analyzing quantitative MRD data in PB at MI: all 20 (100%) pts who remained MRD-positive at MI in the G-chemo arm had low-level MRD (below the limit of quantification) compared with 24/38 (63%) pts in the R-chemo arm. The chemo backbone in the R-chemo arm affected MRD status in PB at EOI giving an MRD response rate of 96% (201/209) after R-bendamustine (B), 93% (100/108) after R-CHOP, and 79% (19/24) after R-CVP. No such effect was seen in the G-chemo arm, where MRD response rates in PB at EOI were high and similar with all three chemo regimens: 96% (187/194), 96% (105/109), and 94% (31/33), respectively. Similarly, in BM, chemo had a large influence on MRD-negative status at EOI in the R-chemo arm (87% [100/115] after R-B, 74% [55/74] after R-CHOP), but negligible impact in the G-chemo arm (93% [109/117] after G-B, 93% [76/82] after G-CHOP). Achievement of MRD negativity at EOI in PB/BM for pts with CR/PR at EOI was associated with longer subsequent PFS, with a hazard ratio of 0.35 (95% CI, 0.22, 0.56; p 〈 0.0001; Figure 1), and comparable effects in both treatment arms. Conclusions: Data from this exploratory analysis support the potential prognostic value of MRD assessment after EOI in FL pts treated with immunochemotherapy. The higher proportion of pts achieving MRD-negative status at MI and EOI, and of pts with low-level MRD among MRD-positives at MI, in the G-chemo arm suggests that G-based induction induces rapid and more effective tumor cell clearance than R-containing therapy. G was more effective than R at enhancing the depth of response to induction therapy in PB and BM, potentially leading to a compensation of differential chemo activity. Future analyses of MRD kinetics during maintenance/follow-up will investigate the pattern and prognostic value of changes in MRD status before relapse, and further evaluate the impact of different chemo regimens. Figure 1. PFS from date of EOI sample by MRD status in PB and/or BM Figure 1. PFS from date of EOI sample by MRD status in PB and/or BM Disclosures Herold: Roche: Honoraria, Other: Grants; Genentech: Other: Grants; Celgene: Honoraria; Gilead: Other: Personal fees from member advisory board. Kneba:AbbVie: Consultancy, Honoraria, Other: Travel grants; Gilead: Consultancy, Honoraria, Other: Travel grants, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: Travel grants; Roche: Consultancy, Honoraria, Other: Travel grants, Research Funding; Amgen: Research Funding; Glaxo-SmithKline: Other: Travel grants. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding. Danesi:F. Hoffmann-La Roche Ltd: Employment. Fingerle-Rowson:Roche: Employment, Equity Ownership. Harbron:Roche: Employment, Equity Ownership; AstraZeneca: Equity Ownership. Mundt:Roche: Employment. Marcus:Takeda: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Hiddemann:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding.

Abstract: This study examines the impact of embedded versus nonembedded (unilateral) news coverage during the U.S. invasion and occupation of Iraq. A content analysis was conduycted of the Washington Post, New York Times, Los Angeles Times, and Chicago Tribune news coverage of the invasion and occupation examining whether embedded and nonembedded new reports were different and, if so, how. News reports were examined for differences in tone toward the military, trust in the military, framing, and authoritativeness. The results of the study revealed significant differences in overall tone toward the military, trust in military personnel, framing, and authoritativeness between embedded and nonembedded articles.

Abstract: TPS363 Background: ADP-A2M4CD8 is an autologous specific peptide enhanced affinity receptor (SPEAR) mixed CD4 and CD8 T-cell product that expresses an engineered T-cell receptor (TCR) designed to target the MAGE-A4 antigen in HLA-A*02-positive patients. These SPEAR T-cells also express wild-type CD8α co-receptors, designed to provide additional functionality to CD4 T-cells. MAGE-A4 expression has been described in several solid tumors, including esophageal and esophagogastric junction (EGJ) cancers[1]. In an ongoing phase 1 study (NCT04044859) of ADP-A2M4CD8 in patients with different tumor types, most adverse events have been consistent with those typically experienced by patients undergoing chemotherapy and/or adoptive T-cell therapies, and as of 2 August 2021, among evaluable patients with esophageal and EGJ cancers, best overall responses were 1 partial response (EGJ), 4 stable disease (2 EGJ, 2 esophageal), and 1 progressive disease (EGJ)[2] . Methods: SURPASS-2 (NCT04752358) is a phase 2, open-label, single-arm trial to assess safety and efficacy of ADP-A2M4CD8 SPEAR T-cells in HLA-A*02–positive patients with advanced esophageal or EGJ cancers that express MAGE-A4 antigen. A total of 45 patients between the ages of 18 and 75 years old will be treated across sites in North America and Europe. Key eligibility criteria include measurable disease per RECIST v1.1; ECOG performance status of 0 or 1; no active autoimmune or immune-mediated disease; no leptomeningeal disease, carcinomatous meningitis, or symptomatic CNS metastases; and ≤2 prior lines of combination or single agent systemic treatment for advanced or metastatic disease before treatment with ADP-A2M4CD8 as the next therapy. Leukapheresis can be performed before initiating or at the end of second-line treatment. Collected T-cells will be transduced with a self-inactivating lentiviral vector expressing the high affinity MAGE-A4-specific TCR and the CD8α co-receptor. Lymphodepleting chemotherapy, consisting of intravenous (IV) cyclophosphamide 600 mg/m 2 /day for 3 days and IV fludarabine 30 mg/m 2 /day for 4 days, will be given approximately 1 week prior to treatment with ADP-A2M4CD8. ADP-A2M4CD8 dose will range between 1 x 10 9 to 10 x 10 9 transduced cells administered by a single IV infusion. The primary endpoint is overall response rate per RECIST v1.1 by an independent radiological assessment committee. Safety evaluations will include adverse events (AEs); serious AEs; incidence, severity, and duration of the AEs of special interest; replication competent lentivirus; and T-cell clonality and insertional oncogenesis. All patients receiving ADP-A2M4CD8 cellular therapy will be followed for 15 years from time of last T-cell infusion for observation of delayed AEs. To date, one site is activated. [1] Ishihara et al. BMC Cancer 20, 606 (2020). [2] Hong et al. E-poster 540P: ESMO (2021). Clinical trial information: NCT04752358.

Abstract: Introduction FL is characterized by the translocation t(14;18), resulting in constitutive overexpression of the key anti-apoptotic protein BCL2. Ven, a selective, potent oral inhibitor of BCL2, has shown profound efficacy combined with anti-CD20 antibodies in chronic lymphocytic leukemia and is in development for treating other hematologic malignancies, including non-Hodgkin lymphoma (NHL). Preclinical and early clinical data in indolent NHL suggest addition of Ven to R or chemo may improve efficacy. The open-label CONTRALTO study (NCT02187861) assessed efficacy and safety of a chemo-free regimen with Ven+R or randomized Ven + standard chemoimmunotherapy regimen BR vs BR for treatment of R/R FL. Methods Pts ≥18 yrs, with confirmed grade (Gr) 1-3a R/R FL, ≥1 line of prior therapy for lymphoma, and adequate hematologic and organ function with no history of B-refractory disease (chemo arms), were assigned at investigators' discretion to receive Ven+R or be randomized to BR +/- Ven, with stratification by 1 vs 0 GELF criteria and ≥ vs 〈 12-mo duration of response (DOR) to prior treatment. The Ven+R arm comprised Ven 800mg daily for 1 yr + R (wk 1-4, mo 4, 6, 8, 10 and 12). After a safety run-in with Ven 600mg, pts in chemo arms were randomized 1:1 to Ven+BR (Ven 800mg daily for 1 yr+ 6 cycles standard BR) or BR. The primary endpoint was 6-mo (end of induction) complete metabolic response rate (CMR) assessed by Lugano 2014 criteria. Secondary endpoints included 1-yr CMR, progression-free survival (PFS), safety, and exploratory biomarker assessments. Pts were followed 6-monthly for safety and efficacy for up to 2 yrs. The final visit was March 15 2018. Results 163 pts were enrolled; 52 received Ven+R, 9 in the safety run-in, 51 Ven+BR, 51 BR (Table 1). Median lines of prior treatment: 3 (1-6) in both Ven-treated arms and 2 (1-4) in BR arm. Ann Arbor stages III/IV: 88%, 73.5%, and 72.5% of pts in Ven+R, Ven+BR and BR arms, respectively. BCL2 expression by IHC and BCL2 translocations were observed in most pts (88% and 81% respectively); expression of MCL1 (1%) and BCLxL (29%) were low. 44 pts (90%) in Ven+BR arm required dose interruptions/modifications of any therapy compared with 21 (42%) in BR and 30 (58%) in Ven+R; most were of Ven: 20 (38.5%) in Ven+R arm and 43 (88%) in Ven+BR. 17 pts (35%) in Ven+BR arm and 2 (4%) in Ven+R discontinued Ven early. 30 pts (61%) in Ven+BR arm required dose interruption/modification of B versus 20 (40%) in BR; 10 pts (20%) in Ven+BR and 2 (4%) in BR discontinued B. Neutropenia and thrombocytopenia were the most common Gr 3-4 adverse events (AEs) overall (Table 2B), and led to dose interruptions/modifications. They were highest in Ven+BR arm (59% neutropenia, 45% thrombocytopenia). Serious AEs were seen more frequently with Ven+BR (Table 2A) than Ven+R or BR; most were infection/infestation events: 22% Ven+BR, 11.5% Ven+R, 8% BR. In Ven+R arm, 17% of pts reached CMR at 6 mo; 25% achieved CMR as best overall response (BOR), of whom all achieved minimal residual disease (MRD) negativity at mid-induction. A population of pts who were non-refractory to prior therapy had improved response (54% overall response rate, 35% CMR as BOR). Six-mo CMR rates were 74% and 68% with Ven+BR and BR, respectively, and were equal at 1 yr (Table 3). PFS analysis did not show a difference between these arms (adjusted HR, 0.69; p=0.2088). Although only 61.2% of pts in Ven+BR arm had ≥90% B dose intensity vs 95.8% in BR arm, efficacy in the 2 arms was comparable in CMR and PFS. Of note, pts maintaining all cycles of Ven+BR had a 6-mo CMR of 100%. Efficacy was comparable in biomarker subgroups, and did not identify clear predictors of response. Conclusion Ven+R had an acceptable toxicity in the population studied; this arm included a high number of pts with refractory status and shorter DOR to prior treatments, potentially leading to modest overall efficacy. Improved response rates and MRD negativity, and longer PFS were observed in a subgroup of pts with non-refractory FL, showing efficacy of Ven+R in FL. Addition of Ven to BR at the dose and schedule studied resulted in increased toxicity (Gr 3-4 cytopenias and gastrointestinal events), leading to dose interruptions/discontinuations, with consequent limitation of overall tolerability. However, despite lower dose intensity of BR in Ven+BR arm, efficacy remained the same between the 2 chemo-containing arms, mandating optimal dose delivery for improved efficacy in combination with chemo in future studies. Disclosures Zinzani: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra Zeneca: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau. Flinn:Portola: Research Funding; Curis: Research Funding; Incyte: Research Funding; Genentech: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Verastem: Consultancy, Research Funding; Forty Seven: Research Funding; Forma: Research Funding; Novartis: Research Funding; Kite: Research Funding; Celgene: Research Funding; ArQule: Research Funding; BeiGene: Research Funding; Infinity: Research Funding; Pharmacyclics: Research Funding; Verastem: Research Funding; Calithera: Research Funding; Agios: Research Funding; Seattle Genetics: Research Funding; Merck: Research Funding; Constellation: Research Funding; Pfizer: Research Funding; Gilead: Research Funding; TG Therapeutics: Research Funding; Janssen: Research Funding. Yuen:Seattle Genetics: Research Funding. Topp:F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding. Rusconi:Celgene: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria. Fleury:Novartis Pharmaceuticals Corporation: Consultancy; Merck: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy; Lundbeck: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; Celgene: Consultancy. Pro:Takeda Pharmaceuticals: Honoraria, Other: Travel expenses; kiowa: Honoraria; Seattle Genetics: Consultancy, Other: Travel expenses, Research Funding; portola: Honoraria. Gritti:Autolus: Consultancy. Crump:F. Hoffmann-La Roche Ltd: Consultancy; Servier Canada: Consultancy; Jansen-Ortho: Consultancy. Samineni:Genentech Inc: Employment, Other: Ownership interests non-PLC. Sinha:F. Hoffmann-La Roche Ltd: Employment. Punnoose:Roche: Equity Ownership; Genentech Inc: Employment. Szafer-Glusman:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Danesi:F. Hoffmann-La Roche Ltd: Employment. Petrich:Abbvie: Employment, Other: Ownership interests PLC. Kornacker:F. Hoffmann-La Roche Ltd: Employment. Humphrey:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Mobasher:Genentech Inc: Employment; F. Hoffmann-La Roche Ltd: Other: Ownership interests non-PLC. Hiddemann:F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system. Methods Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong). Results No histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis. Conclusions We provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.